The Endomembrane System, Endoplasmic Reticulum, and Golgi Apparatus

Overview of the Endomembrane System

  • Definition and Scope:

    • Many of the membrane-bounded organelles in eukaryotic cells belong to the endomembrane system.

    • Organelles included within this system:

    • Nuclear envelope

    • Endoplasmic reticulum (ER)

    • Golgi apparatus

    • Lysosomes

    • Various kinds of vesicles and vacuoles

    • Plasma membrane

  • Key Cellular Tasks:

    • Synthesis of proteins.

    • Transport of proteins into cellular membranes, into internal organelles, or out of the cell entirely.

    • Metabolism and movement of lipids.

    • Detoxification of drugs and poisons.

  • Interconnections and Dynamic Properties:

    • The membranes of the endomembrane system are related either through direct physical continuity or by the transfer of membrane segments via tiny vesicles (sacs composed of membrane).

    • Despite these interconnections, the various membranes are not identical in structure or function.

    • Physical properties such as membrane thickness, molecular composition, and the specific chemical reactions carried out in a given membrane are dynamic and may be modified several times during the membrane's lifespan.

Structure and Compartmentalization of the Endoplasmic Reticulum

  • Scale and Etymology:

    • The endoplasmic reticulum (ER) is an extensive network of membranes that accounts for more than half the total membrane in many eukaryotic cells.

    • The word endoplasmic means "within the cytoplasm," and reticulum is Latin for "little net."

  • Internal Architecture:

    • Consists of a network of membranous tubules and flattened sacs called cisternae (derived from the Latin cisterna, meaning a reservoir for a liquid).

    • The ER membrane separates its internal compartment, the ER lumen (cavity) or cisternal space, from the cytosol.

    • The ER membrane is continuous with the nuclear envelope; as a result, the space between the two membranes of the nuclear envelope is continuous with the lumen of the ER.

  • Subdivisions of the ER:

    • Smooth ER: Outer surface lacks ribosomes.

    • Rough ER: Outer surface is studded with ribosomes, presenting a rough appearance under an electron microscope.

    • Ribosomes are also attached to the cytoplasmic side of the outer membrane of the nuclear envelope, which is continuous with the rough ER.

Functions of the Smooth Endoplasmic Reticulum

  • Overview of Metabolic Roles:

    • The smooth ER functions in diverse metabolic processes that vary depending on the specific cell type.

    • Key functions include lipid synthesis, carbohydrate metabolism, detoxification of drugs and poisons, and storage of calcium ions.

  • Lipid Synthesis:

    • Enzymes of the smooth ER synthesize lipids, including oils, steroids, and new membrane phospholipids.

    • Produces vertebrate sex hormones and the various steroid hormones secreted by the adrenal glands.

    • Cells that synthesize and secrete steroid hormones (e.g., cells in the testes and ovaries) are rich in smooth ER, illustrating a structural adaptation suited to cellular function.

  • Detoxification of Drugs and Poisons:

    • Takes place extensively in liver cells.

    • Chemical Mechanism: Detoxification typically involves adding hydroxyl groups (−OH-\text{OH}) to drug molecules, making them more water-soluble and easier to flush from the body.

    • Substrates: Metabolizes sedatives such as phenobarbital and other barbiturates, alcohol, and numerous other drugs.

    • Proliferation and Drug Tolerance: Repeated exposure to barbiturates, alcohol, and other drugs induces the proliferation of smooth ER and its associated detoxification enzymes, increasing the rate of detoxification.

    • Medical Implications: Enhanced detoxification increases tolerance to the drug, requiring higher doses to achieve a particular effect (e.g., sedation). Because detoxification enzymes possess relatively broad activity, smooth ER proliferation in response to one drug can increase the dosage requirements for other drugs (e.g., barbiturate use can decrease the effectiveness of certain antibiotics).

  • Storage of Calcium Ions (Ca2+\text{Ca}^{2+}):

    • In muscle cells, the smooth ER membrane actively pumps calcium ions (Ca2+\text{Ca}^{2+}) from the cytosol into the ER lumen.

    • When a muscle cell is stimulated by a nerve impulse, calcium ions rush back across the ER membrane into the cytosol, triggering muscle cell contraction.

Functions of the Rough Endoplasmic Reticulum

  • Synthesis and Secretion of Proteins:

    • Ribosomes attached to the rough ER synthesize proteins destined for secretion.

    • Example: Pancreatic cells synthesize the hormone insulin on bound ribosomes in the ER and secrete it into the bloodstream.

    • Translocation Process: As a polypeptide chain grows from a bound ribosome, it is threaded into the ER lumen through a pore formed by a protein complex in the ER membrane.

    • Folding and Glycosylation: The new polypeptide folds into its functional shape inside the ER lumen. Most secretory proteins are glycoproteins (proteins with carbohydrates covalently bonded to them). These carbohydrates are attached to proteins inside the ER lumen by enzymes built into the ER membrane.

    • Sequestration and Transport: Secretory proteins are kept separate from proteins in the cytosol (which are produced by free ribosomes). Secretory proteins depart from the ER wrapped in the membranes of vesicles that bud like bubbles from a specialized region called the transitional ER.

    • Vesicles moving material from one part of the cell to another are called transport vesicles.

  • Membrane Factory for the Cell:

    • The rough ER expands in place by adding membrane proteins and membrane phospholipids directly to its own structure.

    • Polypeptides destined to become membrane proteins are inserted into the ER membrane as they grow from ribosomes, anchored by hydrophobic portions.

    • Enzymes built into the ER membrane assemble membrane phospholipids from precursor molecules located in the cytosol.

    • The ER membrane expands, and portions of it are transferred as transport vesicles to other components of the endomembrane system.

Structure and Directionality of the Golgi Apparatus

  • Role as Shipping and Receiving Center:

    • After departing the ER, many transport vesicles travel to the Golgi apparatus.

    • Functions as a warehouse for receiving, sorting, shipping, and manufacturing cellular products.

    • Products of the ER (such as proteins) are modified, stored, and routed to other destinations.

    • The Golgi apparatus is particularly extensive in cells specialized for secretion.

  • Structural Architecture:

    • Consists of a group of associated, flattened membranous sacs called cisternae, resembling a stack of pita bread.

    • A single cell may contain dozens or hundreds of these stacks.

    • Unlike ER cisternae, Golgi cisternae are not physically connected to one another.

    • The membrane of each cisterna isolates its internal lumenal space from the cytosol.

  • Structural and Functional Polarity:

    • A Golgi stack has distinct directionality; cisternae membranes on opposite sides differ in thickness and molecular composition.

    • cis Face ("on the same side"): Located near the ER; acts as the receiving department. A transport vesicle budding from the ER fuses with the cis membrane, adding its membrane and internal contents to the Golgi.

    • trans Face ("on the opposite side"): Acts as the shipping department. Gives rise to vesicles that pinch off and travel to other cellular locations.


Processing, Manufacturing, and Dynamic Models in the Golgi Apparatus

  • Modification of ER Products:

    • Products of the ER are modified during transit from the cis region to the trans region of the Golgi apparatus.

    • Carbohydrate components of glycoproteins added in the ER are modified in the Golgi by removing certain sugar monomers and substituting others, producing a wide variety of carbohydrate structures.

    • Membrane phospholipids may also undergo modification in the Golgi.

  • Macromolecular Synthesis:

    • The Golgi manufactures certain macromolecules on its own.

    • Many polysaccharides secreted by cells are Golgi products (e.g., pectins and other noncellulose polysaccharides produced in plant Golgi stacks are exported to be incorporated with cellulose in cell walls).

    • Nonprotein products destined for secretion depart from the trans face in transport vesicles, which eventually fuse with the plasma membrane, releasing contents outside the cell and incorporating the vesicle membrane into the plasma membrane.

  • Cisternal Maturation Model:

    • The Golgi manufactures and refines products in sequential stages, with different cisternae containing distinct sets of processing enzymes.

    • Static Model vs. Dynamic Model: Biologists previously viewed the Golgi as a static structure with fixed cisternae that transferred products between stages via vesicles. Research supports the cisternal maturation model, where Golgi cisternae actually progress forward from the cis face to the trans face, modifying and carrying their cargo as they move.

    • Retrograde Vesicle Transport: As cisternae move forward, vesicles transport specific proteins backward to less mature Golgi cisternae or back to the ER where those proteins perform their functional roles.